A Residence-Time Distribution Analysis of the Hydrodynamics within the Intestine in Man during a Regional Single-pass Perfusion with Loc-I-Gut: In-vivo Permeability Estimation

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Abstract
The goal of this study was to determine the most appropriate hydrodynamic model for the Loc‐I‐Gut in‐vivo perfusion system. The general mixing‐tank‐in‐series model, which can approximate single mixing tank and laminar and plug‐flow hydrodynamics, was fitted to the observed experimental residence‐time distribution curves for the non‐absorbable marker [14C]PEG 4000. The residence‐time distribution analysis shows that the hydrodynamics of the perfusion solution within the jejunal segment in man is well approximated by a model containing on average between 1–2 mixing tanks in series. The solution is well mixed when using perfusion rates of 20, 30 and 60 mL min−. The average mean residence time estimates from the fitted residence‐time distribution were 12 ± 7.6, 15 ± 4.2 and 7.7 ± 4.6 min, respectively, at these three perfusion rates. The mean volumes of the segment (Vs) were 25 ± 15, 45 ± 12 and 46 ± 27 mL, respectively. There were no statistical differences between 20, 30 and 60 mL min− in respect of the number of mixing tanks (n) and mean residence times. This residence‐time distribution analysis indicates that the luminal fluid in the Loc‐I‐Gut perfusion system is well‐mixed, and that permeability calculations based on the well‐mixed assumption most closely approximate the actual local (average) membrane permeability within the perfused segment.